Systematic review on effects of experimental orthodontic tooth displacement on brain activation assessed by fMRI.

BACKGROUND: Orthodontic treatment is often accompanied by discomfort and pain in patients, which are believed to be a result of orthodontic tooth displacement caused by the mechanical forces exerted by the orthodontic appliances on the periodontal tissues. These lead to change blood oxygen level dependent response in related brain regions. OBJECTIVE: This systematic review aims to assess the impact of experimental orthodontic tooth displacement on alterations in central nervous system activation assessed by tasked based and resting state fMRI. MATERIALS AND METHODS: A literature search was conducted using online databases, following PRISMA guidelines and the PICO framework. Selected studies utilized magnetic resonance imaging to examine the brain activity changes in healthy participants after the insertion of orthodontic appliances. RESULTS: The initial database screening resulted in 791 studies. Of these, 234 were duplicates and 547 were deemed irrelevant considering the inclusion and exclusion criteria. Of the ten remaining potential relevant studies, two were excluded during full-text screening. Eight prospective articles were eligible for further analysis. The included studies provided evidence of the intricate interplay between orthodontic treatment, pain perception, and brain function. All of the participants in the included studies employed orthodontic separators in short-term experiments to induce tooth displacement during the early stage of orthodontic treatment. Alterations in brain activation were observed in brain regions, functional connectivity and brain networks, predominantly affecting regions implicated in nociception (thalamus, insula), emotion (insula, frontal areas), and cognition (frontal areas, cerebellum, default mode network). CONCLUSIONS: The results suggest that orthodontic treatment influences beyond the pain matrix and affects other brain regions including the limbic system. Furthermore, understanding the orthodontically induced brain activation can aid in development of targeted pain management strategies that do not adversely affect orthodontic tooth movement. Due to the moderate to serious risk of bias and the heterogeneity among the included studies, further clinical trials on this subject are recommended.

Computational Decision Support for PE Diagnosis based on Ventilation Perfusion Ratio.

AIM: The aim of this study is to investigate whether computer-aided, semi-automated 3D lung lobe quantification can support decision-making on PE diagnosis based on the ventilation-perfusion ratio in clinical practice. METHODS: A study cohort of 100 patients (39 male, 61 female, age 64.8±15.8 years) underwent ventilation/perfusion single photon emission computed tomography (V/Q-SPECT/CT) to exclude acute PE on SPECT/CT OPTIMA NM/CT 640 (GE Healthcare). Two 3D lung lobe quantification software tools (Q. Lung: Xeleris 4.0, GE Healthcare and LLQ: Hermes Hybrid 3D Lung Lobar Quantification, Hermes Medical Solutions) were used to evaluate the numerical lobar ventilation/perfusion ratio (VQR) and lobar volume/perfusion ratio (VPR). A test of linearity and equivalence of the two 3D software tools was performed using Pearson, Spearman, quadratic weighted kappa and the mean squared deviation for VPR/VQR. An algorithm was developed that identified PE candidates using ROC analysis. The agreement between the PE findings of an experienced nuclear medicine expert and the calculated PE candidates was represented by the magnitude of the YOUDEN index (J) and the size of the area under the receiver operating curve (AUC). RESULTS: Both 3D software tools showed good comparability. The YOUDEN index for QLUNG(VPR/VQR)/LLQ(VPR/VQR) was in the range from 0.2 to 0.5. The mean AUC averaged over all lung lobes for QLUNG(VPR) was 0.66, CI95%: ±14.0%, for QLUNG(VQR) 0.66, CI95%: ±13.3%, for LLQ(VPR) 0.64, CI95%: ±14.7% and for LLQ(VQR) 0.65, CI95%: ±13.1%. CONCLUSION: This study reveals that 3D software tools are feasible for numerical PE detection. The clinical decision can be supported by using a numerical algorithm based on ROC analysis.

Assessment of Brain Tumour Perfusion Using Early-Phase 18F-FET PET: Comparison with Perfusion-Weighted MRI.

PURPOSE: Morphological imaging using MRI is essential for brain tumour diagnostics. Dynamic susceptibility contrast (DSC) perfusion-weighted MRI (PWI), as well as amino acid PET, may provide additional information in ambiguous cases. Since PWI is often unavailable in patients referred for amino acid PET, we explored whether maps of relative cerebral blood volume (rCBV) in brain tumours can be extracted from the early phase of PET using O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET). PROCEDURE: Using a hybrid brain PET/MRI scanner, PWI and dynamic 18F-FET PET were performed in 33 patients with cerebral glioma and four patients with highly vascularized meningioma. The time interval from 0 to 2 min p.i. was selected to best reflect the blood pool phase in 18F-FET PET. For each patient, maps of MR-rCBV, early 18F-FET PET (0-2 min p.i.) and late 18F-FET PET (20-40 min p.i.) were generated and coregistered. Volumes of interest were placed on the tumour (VOI-TU) and normal-appearing brain (VOI-REF). The correlation between tumour-to-brain ratios (TBR) of the different parameters was analysed. In addition, three independent observers evaluated MR-rCBV and early 18F-FET maps (18F-FET-rCBV) for concordance in signal intensity, tumour extent and intratumoural distribution. RESULTS: TBRs calculated from MR-rCBV and 18F-FET-rCBV showed a significant correlation (r = 0.89, p < 0.001), while there was no correlation between late 18F-FET PET and MR-rCBV (r = 0.24, p = 0.16) and 18F-FET-rCBV (r = 0.27, p = 0.11). Visual rating yielded widely agreeing findings or only minor differences between MR-rCBV maps and 18F-FET-rCBV maps in 93 % of the tumours (range of three independent raters 91-94%, kappa among raters 0.78-1.0). CONCLUSION: Early 18F-FET maps (0-2 min p.i.) in gliomas provide similar information to MR-rCBV maps and may be helpful when PWI is not possible or available. Further studies in gliomas are needed to evaluate whether 18F-FET-rCBV provides the same clinical information as MR-rCBV.

GABAA receptor availability relates to emotion-induced BOLD responses in the medial prefrontal cortex: simultaneous fMRI/PET with [11C]flumazenil.

Introduction: The fMRI BOLD response to emotional stimuli highlighting the role of the medial prefrontal cortex (MPFC) has been thoroughly investigated. Recently, the relationship between emotion processing and GABA levels has been studied using MPFC proton magnetic resonance spectroscopy (1H-MRS). However, the role of GABAA receptors in the MPFC during emotion processing remains unexplored. Methods: Using [11C]flumazenil PET, we investigated the relationship between the binding potential of GABAA receptors and emotion processing as measured using simultaneous fMRI BOLD. We hypothesized a correlation between the percent signal change in the BOLD signal and the binding potential of GABAA receptors in the MPFC. In a combined simultaneous fMRI and [11C]flumazenil-PET study, we analyzed the data from 15 healthy subjects using visual emotional stimuli. Our task comprised two types of emotional processing: passive viewing and appraisal. Following the administration of a bolus plus infusion protocol, PET and fMRI data were simultaneously acquired in a hybrid 3 T MR-BrainPET. Results: We found a differential correlation of BOLD percent signal change with [11C]flumazenil binding potential in the MPFC. Specifically, [11C]flumazenil binding potential in the ventromedial prefrontal cortex (vMPFC) correlated with passive viewing of emotionally valenced pictures. In contrast, the [11C]flumazenil binding potential and the BOLD signal induced by picture appraisal did show a correlation in the paracingulate gyrus. Conclusion: Our data deliver first evidence for a relationship between MPFC GABAA receptors and emotion processing in the same region. Moreover, we observed that GABAA receptors appear to play different roles in emotion processing in the vMPFC (passive viewing) and paracingulate gyrus (appraisal).

The impact of brain lesions on health-related quality of life in patients with WHO CNS grade 3 or 4 glioma: a lesion-function and resting-state fMRI analysis.

PURPOSE: In glioma patients, tumor development and multimodality therapy are associated with changes in health-related quality of life (HRQoL). It is largely unknown how different types and locations of tumor- and treatment-related brain lesions, as well as their relationship to white matter tracts and functional brain networks, affect HRQoL. METHODS: In 121 patients with pretreated gliomas of WHO CNS grades 3 or 4, structural MRI, O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET, resting-state functional MRI (rs-fMRI) and self-reported HRQoL questionnaires (EORTC QLQ-C30/BN20) were obtained. Resection cavities, T1-enhancing lesions, T2/FLAIR hyperintensities, and lesions with pathologically increased FET uptake were delineated. Effects of tumor lateralization, involvement of white matter tracts or resting-state network nodes by different types of lesions and within-network rs-fMRI connectivity were analyzed in terms of their interaction with HRQoL scores. RESULTS: Right hemisphere gliomas were associated with significantly less favorable outcomes in physical, role, emotional and social functioning, compared with left-sided tumors. Most functional HRQoL scores correlated significantly with right-sided white-matter tracts involvement by T2/FLAIR hyperintensities and with loss of within-network functional connectivity of right-sided nodes. Tumors of the left hemisphere caused significantly more communication deficits. CONCLUSION: In pretreated high-grade gliomas, right hemisphere lesions are associated with reduced HRQoL scores in most functional domains except communication ability, compared to tumors of the left hemisphere. These relationships are mainly observed for T2/FLAIR lesions involving structural and functional networks in the right hemisphere. The data suggest that sparing the right hemisphere from treatment-related tissue damage may improve HRQoL in glioma patients.

Increasing striatal dopamine release through repeated bouts of theta burst transcranial magnetic stimulation of the left dorsolateral prefrontal cortex. A 18F-desmethoxyfallypride positron emission tomography study.

Introduction: Transcranial Magnetic Stimulation (TMS) can modulate fronto-striatal connectivity in the human brain. Here Positron Emission Tomography (PET) and neuro-navigated TMS were combined to investigate the dynamics of the fronto-striatal connectivity in the human brain. Employing 18F-DesmethoxyFallypride (DMFP) - a Dopamine receptor-antagonist - the release of endogenous dopamine in the striatum in response to time-spaced repeated bouts of excitatory, intermittent theta burst stimulation (iTBS) of the Left-Dorsolateral Prefrontal Cortex (L-DLPFC) was measured. Methods: 23 healthy participants underwent two PET sessions, each one with four blocks of iTBS separated by 30 minutes: sham (control) and verum (90% of individual resting motor threshold). Receptor Binding Ratios were collected for sham and verum sessions across 37 time frames (about 130 minutes) in striatal sub-regions (Caudate nucleus and Putamen). Results: Verum iTBS increased the dopamine release in striatal sub-regions, relative to sham iTBS. Dopamine levels in the verum session increased progressively across the time frames until frame number 28 (approximately 85 minutes after the start of the session and after three iTBS bouts) and then essentially remained unchanged until the end of the session. Conclusion: Results suggest that the short-timed iTBS protocol performed in time-spaced blocks can effectively induce a dynamic dose dependent increase in dopaminergic fronto-striatal connectivity. This scheme could provide an alternative to unpleasant and distressing, long stimulation protocols in experimental and therapeutic settings. Specifically, it was demonstrated that three repeated bouts of iTBS, spaced by short intervals, achieve larger effects than one single stimulation. This finding has implications for the planning of therapeutic interventions, for example, treatment of major depression.

The effect of surveillance for differentiated thyroid carcinoma in childhood cancer survivors on survival rates: a decision-tree-based analysis.

Background: Childhood cancer survivors (CCS) who received radiation therapy exposing the thyroid gland are at increased risk of developing differentiated thyroid cancer (DTC). Therefore, the International Guideline Harmonization Group (IGHG) on late effects of childhood cancer therefore recommends surveillance. It is unclear whether surveillance reduces mortality. Aim: The aim of this study was to compare four strategies for DTC surveillance in CCS with the aim of reducing mortality: Strategy-1, no surveillance; Strategy-2, ultrasound alone; Strategy-3, ultrasound followed by fine-needle biopsy (FNB); Strategy-4, palpation followed by ultrasound and FNB. Materials and methods: A decision tree was formulated with 10-year thyroid cancer-specific survival as the endpoint, based on data extracted from literature. Results: It was calculated that 12.6% of CCS will develop DTC. Using Strategy-1, all CCS with DTC would erroneously not be operated upon, but no CCS would have unnecessary surgery. With Strategy-2, all CCS with and 55.6% of CCS without DTC would be operated. Using Strategy-3, 11.1% of CCS with DTC would be correctly operated upon, 11.2% without DTC would be operated upon and 1.5% with DTC would not be operated upon. With Strategy-4, these percentages would be 6.8, 3.9 and 5.8%, respectively. Median 10-year survival rates would be equal across strategies (0.997). Conclusion: Different surveillance strategies for DTC in CCS all result in the same high DTC survival. Therefore, the indication for surveillance may lie in a reduction of surgery-related morbidity rather than DTC-related mortality. In accordance with the IGHG guidelines, the precise strategy should be decided upon in a process of shared decision-making.

Body Composition as a Predictor of the Survival in Anal Cancer.

Background and aim: Sarcopenia and body composition parameters such as visceral and subcutaneous adipose tissue and visceral-to-subcutaneous adipose tissue ratio have been shown to be relevant biomarkers for prognosis in patients with different types of cancer. However, these findings have not been well studied in anal cancer to date. Therefore, the aim of this study was to evaluate the prognostic value of different body composition parameters in patients undergoing radiation therapy for the treatment of anal cancer with curative intent. Material and Methods: After approval by the institutional ethical committee, we retrospectively identified 81 patients in our local registry, who received radical intensity-modulated radiotherapy for the management of anal squamous cell cancer (ASCC). Clinical information, including body mass index (BMI), survival, and toxicities outcome, were retrieved from the local hospital registry. Based on the pre-therapeutic computer tomography (CT), we measured the total psoas muscle area, visceral adipose tissue area (VAT), subcutaneous adipose tissue area (SAT), and visceral-to-subcutaneous adipose tissue area ratio (VSR). In addition to the classical prognostic factors as T-stage, N-stage, gender, and treatment duration, we analyzed the impact of body composition on the prognosis in univariate and multivariate analyses. Results: Sarcopenia was not associated with increased mortality in anal cancer patients, whereas increased BMI (≥27 kg/m2) and VSR (≥0.45) were significantly associated with worsened overall survival and cancer-specific survival in both univariate and multivariate analyses. VSR-not BMI-was statistically higher in males. Sarcopenia and VSR ≥ 0.45 were associated with advanced T-stages. None of the body composition parameters resulted in a significant increase in treatment-related toxicities. Conclusion: BMI and visceral adiposity are independent prognostic factors for the survival of patients with anal cancer. Measurements to treat adiposity at the time of diagnosis may be needed to improve the survival outcomes for the affected patients.

Static FET PET radiomics for the differentiation of treatment-related changes from glioma progression.

PURPOSE: To investigate the potential of radiomics applied to static clinical PET data using the tracer O-(2-[18F]fluoroethyl)-L-tyrosine (FET) to differentiate treatment-related changes (TRC) from tumor progression (TP) in patients with gliomas. PATIENTS AND METHODS: One hundred fifty-one (151) patients with histologically confirmed gliomas and post-therapeutic progressive MRI findings according to the response assessment in neuro-oncology criteria underwent a dynamic amino acid PET scan using the tracer O-(2-[18F]fluoroethyl)-L-tyrosine (FET). Thereof, 124 patients were investigated on a stand-alone PET scanner (data used for model development and validation), and 27 patients on a hybrid PET/MRI scanner (data used for model testing). Mean and maximum tumor to brain ratios (TBRmean, TBRmax) were calculated using the PET data from 20 to 40 min after tracer injection. Logistic regression models were evaluated for the FET PET parameters TBRmean, TBRmax, and for radiomics features of the tumor areas as well as combinations thereof to differentiate between TP and TRC. The best performing models in the validation dataset were finally applied to the test dataset. The diagnostic performance was assessed by receiver operating characteristic analysis. RESULTS: Thirty-seven patients (25%) were diagnosed with TRC, and 114 (75%) with TP. The logistic regression model comprising the conventional FET PET parameters TBRmean and TBRmax resulted in an AUC of 0.78 in both the validation (sensitivity, 64%; specificity, 80%) and the test dataset (sensitivity, 64%; specificity, 80%). The model combining the conventional FET PET parameters and two radiomics features yielded the best diagnostic performance in the validation dataset (AUC, 0.92; sensitivity, 91%; specificity, 80%) and demonstrated its generalizability in the independent test dataset (AUC, 0.85; sensitivity, 81%; specificity, 70%). CONCLUSION: The developed radiomics classifier allows the differentiation between TRC and TP in pretreated gliomas based on routinely acquired static FET PET scans with a high diagnostic accuracy.

Two Decades of Brain Tumour Imaging with O-(2-[18F]fluoroethyl)-L-tyrosine PET: The Forschungszentrum Jülich Experience.

O-(2-[18F]fluoroethyl)-L-tyrosine (FET) is a widely used amino acid tracer for positron emission tomography (PET) imaging of brain tumours. This retrospective study and survey aimed to analyse our extensive database regarding the development of FET PET investigations, indications, and the referring physicians' rating concerning the role of FET PET in the clinical decision-making process. Between 2006 and 2019, we performed 6534 FET PET scans on 3928 different patients against a backdrop of growing demand for FET PET. In 2019, indications for the use of FET PET were as follows: suspected recurrent glioma (46%), unclear brain lesions (20%), treatment monitoring (19%), and suspected recurrent brain metastasis (13%). The referring physicians were neurosurgeons (60%), neurologists (19%), radiation oncologists (11%), general oncologists (3%), and other physicians (7%). Most patients travelled 50 to 75 km, but 9% travelled more than 200 km. The role of FET PET in decision-making in clinical practice was evaluated by a questionnaire consisting of 30 questions, which was filled out by 23 referring physicians with long experience in FET PET. Fifty to seventy per cent rated FET PET as being important for different aspects of the assessment of newly diagnosed gliomas, including differential diagnosis, delineation of tumour extent for biopsy guidance, and treatment planning such as surgery or radiotherapy, 95% for the diagnosis of recurrent glioma, and 68% for the diagnosis of recurrent brain metastases. Approximately 50% of the referring physicians rated FET PET as necessary for treatment monitoring in patients with glioma or brain metastases. All referring physicians stated that the availability of FET PET is essential and that it should be approved for routine use. Although the present analysis is limited by the fact that only physicians who frequently referred patients for FET PET participated in the survey, the results confirm the high relevance of FET PET in the clinical diagnosis of brain tumours and support the need for its approval for routine use.

Intensity-Modulated Radiotherapy Associated With Improved Survival Outcome in Anal Cancer.

Purpose: To describe the survival and toxicity outcome from a single-centre experience in patients with squamous cell cancer of the anal canal (SCC-AC), related to the impact of technological advances in diagnostics and radiation techniques. Material and Methods: A retrospective cohort study was performed after the approval of the institutional ethical committee (EK 478-21). We identified 142 patients in our registry, who received radical treatment for SCC-AC between 2000 and 2020. Fifty-five patients had FDG PET/CT for initial staging and target volume delineation, 87.33% received concomitant chemoradiotherapy (CRT), 64 patients were treated with 3-dimensional conformal radiotherapy (3DRT) between 2000-2009, and 78 patients with intensity-modulated radiotherapy (IMRT) between 2009-2020. Endpoints for the analysis included locoregional relapse-free survival (LRFS), disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS). Acute and late toxicities were also reported. Results: At a median follow-up of 31.2 months, the median overall survival was 135 months, 5-year LRFS was 73.1%, 5-year DFS was 65.3%, and 5-year CSS was 75.3%. The use of IMRT was associated with shorter treatment duration. In the univariate analysis, IMRT was associated with significantly improved DFS and CSS for the whole cohort and significantly improved DFS, OS, and CSS for patients who received CRT. In the multivariate analysis, IMRT was associated with the improvement of all survival paraments. The use of FDG PET/CT did not translate into an improvement in the survival outcomes in both univariate and multivariate analyses. Grade-3 and more dermatological toxicities occurred less frequently, but hematological toxicities were more frequent in the IMRT-group. Late side effects and colostomies were less frequently reported in the IMRT group. Conclusion: The use of IMRT in the management of SCC-AC was associated with improvement of the oncological outcomes with improved toxicity profiles in this long-term single-centre experience.

Assessment of the lymphatic system by indirect lymphography in patients with post-thrombotic syndrome.

OBJECTIVE: Alterations in lower extremity lymph drainage caused by chronic venous obstruction (CVO) have not been well studied, partially because of a lack of standardized imaging modalities to assess the quality of lymphatic drainage in the lower extremities of patients with post-thrombotic syndrome (PTS). However, these changes are likely to have an impact on the severity of the disease and clinical outcomes of interventions. In the present study, we investigated the feasibility and diagnostic value of preintervention indirect lymphography in patients with CVO and their pre- and postintervention Villalta scores. METHODS: A total of 17 patients (21 limbs) with iliofemoral and caval CVO were included in the study between 2017 and 2018. The deep and superficial lymphatic vessels in both legs were assessed before venous recanalization and stenting. The quality of lymphatic flow was compared between the legs with CVO and healthy legs. Moreover, the correlation between the lymphatic changes and clinical severity of PTS was evaluated using the Villalta score and CEAP (Clinical, Etiology, Anatomy, and Pathophysiology) classification. RESULTS: The mean patient age was 44 ± 12 years, and 10 patients (59%) were women. The patients had undergone treatment at a mean of 25 ± 6 months after their first episode of deep vein thrombosis. Five patients (29%) had had recurrent deep vein thrombosis. The mean pre- and postinterventional Villalta score was 10.5 ± 1.46 and 9.27 ± 1.12, respectively (P = .0096). Using the CEAP classification, four legs were class 5, seven were class 4, and three each were class 3 and 2. The primary and secondary patency rate was 70.5% and 82.5% after a mean follow-up of 18 months, respectively. Indirect lymphography of the superficial and deep lymphatic systems was completed before intervention in both legs for all 17 patients (21 legs). According to the qualitative criteria, abnormal lymphatic vessel function was found in 35.2% of the superficial and 58.8% of the deep lymphatic vessels of the affected legs. Further analysis revealed abnormal function of the deep lymphatic vessels in all patients with moderate to severe PTS according to the Villalta score. CONCLUSIONS: Indirect lymphography is a feasible diagnostic tool to use for the evaluation of the function of lymphatic vessels. Impaired drainage of the deep lymphatic system was found in all our patients with moderate to severe PTS. The clinical significance of these lymphatic changes is not clear; however, an association between clinical severity and outcomes is possible.

Cost Effectiveness of 18F-FET PET for Early Treatment Response Assessment in Glioma Patients After Adjuvant Temozolomide Chemotherapy.

In light of increasing health-care costs, higher medical expenses should be justified socioeconomically. Therefore, we calculated the effectiveness and cost effectiveness of PET using the radiolabeled amino acid O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) compared with conventional MRI for early identification of responders to adjuvant temozolomide chemotherapy. A recently published study in isocitrate dehydrogenase wild-type glioma patients suggested that 18F-FET PET parameter changes predicted a significantly longer survival already after 2 cycles whereas MRI changes were not significant. Methods: To determine the effectiveness and cost effectiveness of serial 18F-FET PET imaging, we analyzed published clinical data and calculated the associated costs from the perspective of the German Statutory Health Insurance system. Based on a decision-tree model, the effectiveness of 18F-FET PET and MRI was calculated-that is, the probability to correctly identify a responder as defined by an overall survival of at least 15 mo. To determine the cost effectiveness, the incremental cost effectiveness ratio (ICER) was calculated-that is, the cost for each additionally identified responder by 18F-FET PET who would have remained undetected by MRI. The robustness of the results was tested by deterministic and probabilistic Monte Carlo sensitivity analyses. Results: Compared with MRI, 18F-FET PET increased the rate of correctly identified responders to chemotherapy by 26%; thus, 4 patients needed to be examined by 18F-FET PET to identify 1 additional responder. Considering the respective costs for serial 18F-FET PET and MRI, the ICER resulted in €4,396.83 for each additional correctly identified responder by 18F-FET PET. Sensitivity analyses confirmed the robustness of the results. Conclusion: In contrast to conventional MRI, the model suggests that 18F-FET PET is cost-effective in terms of ICER values. Considering the high cost of temozolomide, the integration of 18F-FET PET has the potential to avoid premature chemotherapy discontinuation at reasonable cost.

Teaching of Nuclear Cardiology in Times of Pandemic: Transfer of a Case-based Interactive Course from Classroom to Distance Learning.

AIM: While methods of independent study, such as problem-based learning, have been shown beneficial to students' learning outcome and motivation to self-educate, these concepts are currently challenged by the pandemic. The aim of the current study was the evaluation of the transfer of an interactive nuclear cardiology teaching module to an online, distance learning setting. METHODS: Two-hundred-forty medical students completed and evaluated the teaching module in a classroom and 127 students in the distance learning setting. RESULTS: The interactive, problem-based teaching module was transferred well into the distance learning setting during the pandemic. However, while the presented results suggest that distance learning is a good substitute for classroom teaching when in-person teaching is not possible, the distance teaching module was perceived less efficient in its course didactics, demands as well as applicability than the same module in a classroom setting. CONCLUSION: Although distance learning thus cannot entirely replace classroom education, it does provide a well-suited alternative method to teach particularly nuclear medicine and medicine in general. Future applications should offer introductory sessions, provide learning materials in advance and slow down the teaching pace to facilitate online, distance learning.

Evaluation of new endodontic tooth models in clinical education from the perspective of students and demonstrators.

BACKGROUND: The quality of root canal treatments performed by undergraduate students is often unsatisfactory questioning the current methods of teaching. Based on treatment errors made by students participating the endodontic courses at RWTH Aachen University (Germany), new radiopaque artificial root canal treatment models (DRSK RCT; incisor, premolar, molar) were designed and developed. The aim of the study was to evaluate these models by groups of students and demonstrators. METHODS: A total number of 60 students and seven demonstrators from a single institution (RWTH Aachen) participated in this study. They performed endodontic treatments on either initial versions of the DRSK RCT or modified versions. The initial versions were evaluated by students (n = 25) and demonstrators (n = 7). The obtained questionnaire was conducted as 7-point Likert-Scale covering the topics material properties, feeling while performing exercises and perception of its closeness to reality via 19 items (students) and 21 items (demonstrators). According to the evaluations several alterations were applied to the DRSK RCT, the whole study was repeated and evaluated by different students (n = 35) and the same demonstrators (n = 7). Additionally, the demonstrators blindly evaluated the quality of root canal treatments performed by the students (n = 35) on the modified DRSK RCT. Comparisons between the initial versions and the modified versions were calculated using Chi-squared tests. RESULTS: Students as well as demonstrators positively evaluated both variants of the DRSK RCT with especially high ratings in the overall evaluation. Students' rating of the pulp anatomy significantly increased from 5.4 ± 1.1 (mean ± SD) to 5.9 ± 0.9 (mean ± SD; p < 0.05) for the modified model. Likewise, students felt that the ability to flare root canals improved after alterations have been applied. Ratings significantly increased from 4.8 ± 1.6 (mean ± SD) to 5.6 ± 1.0 (mean ± SD; p < 0.05). CONCLUSION: The results indicate that the DRSK RCT is a promising candidate to be used as an alternative to extracted teeth or as an additional tool for improving dental education. However, some limitations of our analysis have to be considered.

Use of full-dose contrast-enhanced CT for extrahepatic staging using Gallium-68-DOTATATE PET/CT in patients with neuroendocrine tumors.

PURPOSE: Studies have demonstrated that positron emission tomography/computed tomography (PET/CT) with Gallium-68 (68Ga)-labeled somatostatin analogues are effective at detecting metastatic disease in neuroendocrine tumors (NET), especially extrahepatic metastases. However, PET in combination with full-dose contrast-enhanced CT (ceCT) exposes patients to higher radiation (~25 mSv). The use of non-contrast-enhanced low-dose CT (ldCT) can reduce radiation to about 10 mSv and may avoid contrast-induced side effects. This study seeks to determine whether ceCT could be omitted from NET assessments. METHODS: We retrospectively compared the performance of PET/ldCT versus PET/ceCT in 54 patients (26 male, 28 female) who had undergone a 68Ga-DOTATATE PET/CT. The selection criteria were as follows: available ldCT and ceCT, histologically confirmed NET, and follow-up of at least 6 months (median, 12.6 months; range, 6.1-23.2 months). The PET/ldCT and PET/ceCT images were analyzed separately. We reviewed metastases in the lungs, bones, and lymph nodes. The results were compared with the reference standard (clinical follow-up data). RESULTS: The PET/ceCT scans detected 139 true-positive bone lesions compared with 140 lesions detected by the PET/ldCT scans, 106 true-positive lymph node metastases (PET/ceCT) compared with 90 metastases detected by the PET/ldCT scans, and 26 true-positive lung lesions (PET/ceCT) compared with 6 lesions detected by the PET/ldCT scans. The overall lesion-based sensitivity for full-dose PET/ceCT was 97%, specificity 86%, negative predictive value (NPV) 93%, and positive predictive value (PPV) 93%. The overall lesion-based sensitivity for PET/ldCT was 85%, specificity 73%, NPV 72%, and PPV 85%. CONCLUSION: This study presents the first evidence that ceCT should not be omitted from extrahepatic staging using 68Ga-DOTATATE PET/CT in patients with NET. ceCT alone can be used as a follow-up to reduce radiation exposure when the patient has already undergone PET/ceCT and suffers from non-DOTATATE-avid NET.

18F-Fluorothymidine PET is an early and superior predictor of progression-free survival following chemoimmunotherapy of diffuse large B cell lymphoma: a multicenter study.

PURPOSE: To determine whether interim 3'-deoxy-3'-[18F]fluorothymidine (iFLT) PET/CT is a superior predictor of progression-free survival (PFS) compared with interim 18F-fluorodeoxyglucose (iFDG) PET/CT in patients with diffuse large B cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH). METHODS: Ninety-two prospectively enrolled patients with DLBCL underwent both FLT-PET/CT and FDG-PET/CT 18-24 days after two cycles of R-CHOP/R-EPOCH. Deauville-criteria, PERCIST1.0, standardized uptake value (SUV), total lesion glycolysis (TLG), and metabolic tumor volume were used to interpret iFDG-PET/CT while dichotomous visual interpretation was used to interpret iFLT-PET/CT and the results were compared with the 3- and 5-year PFS. RESULTS: iFLT-PET/CT was negative in 67 (73%) and positive in 25 (27%) patients. iFDG-PET/CT by Deauville criteria was negative (Deauville scores [DS] of 1-3) in 53 (58%) and positive (DS = 4-5) in 39 (42%) patients. Of the 67 iFLT-PET/CT-negative patients, 7 (10.4%) progressed at a median of 14.1 months whereas 14/25 (56.0%) iFLT-PET/CT-positive patients progressed at a median of 7.8 months (P < .0001). Of the 53 Deauville-negative patients, 9 (17.0%) progressed at a median of 14.1 months whereas 12/39 (30.8%) Deauville-positive patients progressed at a median of 5.6 months (P = .11). In multivariate analysis, including iFLT-PET/CT, PERCIST, interim TLG, and interim SUVmax, only iFLT-PET/CT was an independent predictor for 3- and 5-year PFS (P < .0001 and P = .001, respectively). CONCLUSIONS: In patients with DLBCL given R-CHOP/R-EPOCH, iFLT-PET/CT is a superior independent predictor of outcome compared with iFDG-PET/CT.

Induction of Contralateral Hepatic Hypertrophy by Unilobar Yttrium-90 Transarterial Radioembolization versus Portal Vein Embolization: An Animal Study.

PURPOSE: To compare hepatic hypertrophy in the contralateral lobe achieved by unilobar transarterial radioembolization (TARE) versus portal vein embolization (PVE) in a swine model. METHODS: After an escalation study to determine the optimum dose to achieve hypertrophy after unilobar TARE in 4 animals, 16 pigs were treated by TARE (yttrium-90 resin microspheres) or PVE (lipiodol/n-butyl cyanoacrylate). Liver volume was calculated based on CT before treatment and during 6 months of follow-up. Independent t-test (P < .05) was used to compare hypertrophy. The relationship between hypertrophy after TARE and absorbed dose was calculated using the Pearson correlation. RESULTS: At 2 and 4 weeks after treatment, a significantly higher degree of future liver remnant hypertrophy was observed in the PVE group versus the TARE group, with a median volume gain of 31% (interquartile range [IQR]: 16%-66%) for PVE versus 23% (IQR: 6%-36%) for TARE after 2 weeks and 51% (IQR: 47%-69%) for PVE versus 29% (IQR: 20%-50%) for TARE after 4 weeks. After 3 and 6 months, hypertrophy converged without a statistically significant difference, with a volume gain of 103% (IQR: 86%-119%) for PVE versus 82% (IQR: 70%-96%) for TARE after 3 months and 115% (IQR: 70%-46%) for PVE versus 86% (IQR: 58%-111%) for TARE after 6 months. A strong correlation was observed between radiation dose (median 162 Gy, IQR: 139-175) and hypertrophy. CONCLUSIONS: PVE resulted in rapid hypertrophy within 1 month of the procedure, followed by a plateau, whereas TARE resulted in comparable hypertrophy by 3-6 months. TARE-induced hypertrophy correlated with radiation absorbed dose.

Current trends in the use of O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) in neurooncology.

The diagnostic potential of PET using the amino acid analogue O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) in brain tumor diagnostics has been proven in many studies during the last two decades and is still the subject of multiple studies every year. In addition to standard magnetic resonance imaging (MRI), positron emission tomography (PET) using [18F]FET provides important diagnostic data concerning brain tumor delineation, therapy planning, treatment monitoring, and improved differentiation between treatment-related changes and tumor recurrence. The pharmacokinetics, uptake mechanisms and metabolism have been well described in various preclinical studies. The accumulation of [18F]FET in most benign lesions and healthy brain tissue has been shown to be low, thus providing a high contrast between tumor tissue and benign tissue alterations. Based on logistic advantages of F-18 labelling and convincing clinical results, [18F]FET has widely replaced short lived amino acid tracers such as L-[11C]methyl-methionine ([11C]MET) in many centers across Western Europe. This review summarizes the basic knowledge on [18F]FET and its contribution to the care of patients with brain tumors. In particular, recent studies about specificity, possible pitfalls, and the utility of [18F]FET PET in tumor grading and prognostication regarding the revised WHO classification of brain tumors are addressed.